5XVU
Crystal structure of the protein kinase CK2 catalytic domain from Plasmodium falciparum bound to ATP
Summary for 5XVU
| Entry DOI | 10.2210/pdb5xvu/pdb |
| Descriptor | Casein kinase 2, alpha subunit, SULFATE ION, CHLORIDE ION, ... (7 entities in total) |
| Functional Keywords | casein kinase 2 plasmodium falciparum kinase, transferase |
| Biological source | Plasmodium falciparum (isolate 3D7) |
| Total number of polymer chains | 3 |
| Total formula weight | 121577.53 |
| Authors | El Sahili, A.,Lescar, J.,Ruiz-Carrillo, D.,Lin, J.Q. (deposition date: 2017-06-28, release date: 2017-07-12, Last modification date: 2023-11-22) |
| Primary citation | Ruiz-Carrillo, D.,Lin, J.Q.,El Sahili, A.,Wei, M.,Sze, S.K.,Cheung, P.C.F.,Doerig, C.,Lescar, J. The protein kinase CK2 catalytic domain from Plasmodium falciparum: crystal structure, tyrosine kinase activity and inhibition. Sci Rep, 8:7365-7365, 2018 Cited by PubMed Abstract: Malaria causes every year over half-a-million deaths. The emergence of parasites resistant to available treatments makes the identification of new targets and their inhibitors an urgent task for the development of novel anti-malaria drugs. Protein kinase CK2 is an evolutionary-conserved eukaryotic serine/threonine protein kinase that in Plasmodium falciparum (PfCK2) has been characterized as a promising target for chemotherapeutic intervention against malaria. Here we report a crystallographic structure of the catalytic domain of PfCK2α (D179S inactive single mutant) in complex with ATP at a resolution of 3.0 Å. Compared to the human enzyme, the structure reveals a subtly altered ATP binding pocket comprising five substitutions in the vicinity of the adenine base, that together with potential allosteric sites, could be exploited to design novel inhibitors specifically targeting the Plasmodium enzyme. We provide evidence for the dual autophosphorylation of residues Thr and Tyr of PfCK2. We also show that CX4945, a human CK2 inhibitor in clinical trials against solid tumor cancers, is effective against PfCK2 with an IC of 13.2 nM. PubMed: 29743645DOI: 10.1038/s41598-018-25738-5 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3 Å) |
Structure validation
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